Meadows Sarah K, Dressman Holly K, Muramoto Garrett G, Himburg Heather, Salter Alice, Wei ZhengZheng, Ginsburg Geoffrey S, Chao Nelson J, Nevins Joseph R, Chute John P
Division of Cellular Therapy, Duke University Medical Center, Durham, North Carolina, United States of America.
PLoS One. 2008 Apr 2;3(4):e1912. doi: 10.1371/journal.pone.0001912.
Previous work has demonstrated the potential for peripheral blood (PB) gene expression profiling for the detection of disease or environmental exposures.
We have sought to determine the impact of several variables on the PB gene expression profile of an environmental exposure, ionizing radiation, and to determine the specificity of the PB signature of radiation versus other genotoxic stresses. Neither genotype differences nor the time of PB sampling caused any lessening of the accuracy of PB signatures to predict radiation exposure, but sex difference did influence the accuracy of the prediction of radiation exposure at the lowest level (50 cGy). A PB signature of sepsis was also generated and both the PB signature of radiation and the PB signature of sepsis were found to be 100% specific at distinguishing irradiated from septic animals. We also identified human PB signatures of radiation exposure and chemotherapy treatment which distinguished irradiated patients and chemotherapy-treated individuals within a heterogeneous population with accuracies of 90% and 81%, respectively.
We conclude that PB gene expression profiles can be identified in mice and humans that are accurate in predicting medical conditions, are specific to each condition and remain highly accurate over time.
先前的研究已经证明外周血(PB)基因表达谱在检测疾病或环境暴露方面具有潜力。
我们试图确定几个变量对环境暴露(电离辐射)的PB基因表达谱的影响,并确定辐射的PB特征相对于其他基因毒性应激的特异性。基因型差异和PB采样时间均未降低PB特征预测辐射暴露的准确性,但性别差异确实影响了最低剂量(50 cGy)辐射暴露预测的准确性。还生成了脓毒症的PB特征,发现辐射的PB特征和脓毒症的PB特征在区分受辐照动物和脓毒症动物方面具有100%的特异性。我们还确定了辐射暴露和化疗治疗的人类PB特征,它们在异质人群中分别以90%和81%的准确率区分受辐照患者和接受化疗的个体。
我们得出结论,在小鼠和人类中可以识别出PB基因表达谱,这些表达谱在预测医疗状况方面是准确的,对每种状况具有特异性,并且随着时间的推移保持高度准确。